Antiviral Effects of 5-Aminolevulinic Acid Phosphate against Classical Swine Fever Virus: In Vitro and In Vivo Evaluation.

Shizuka Hirose,Kenjiro Inui,Taksoo Kim,Yoshihiro Sakoda,Tohru Tanaka,Keiichiro Yoshimoto,Loc Tan Huynh,Takahiro Hiono,Norikazu Isoda

doi:10.3390/pathogens11020164

Abstract

The inhibitory effects of 5-aminolevulinic acid phosphate (5-ALA), an important amino acid for energy production in the host, against viral infections were previously reported. Here, the antiviral effects of 5-ALA against classical swine fever virus (CSFV) belonging to the genus Pestivirus in the Flaviviridae family and its possible mechanisms were investigated. CSFV replication was suppressed in swine cells supplemented with 5-ALA or its metabolite, protoporphyrin IX (PPIX). The infectivity titer of CSFV was decreased after mixing with PPIX extracellularly. In addition, the activities of the replication cycle were decreased in the presence of PPIX based on the CSFV replicon assay. These results showed that PPIX exerted antiviral effects by inactivating virus particles and inhibiting the replication cycle. To evaluate the in vivo efficacy of 5-ALA, pigs were supplemented daily with 5-ALA for 1 week before virus inoculation and then inoculated with a virulent CSFV strain at the 107.0 50% tissue culture infectious dose. The clinical scores of the supplemented group were significantly lower than those of the nonsupplemented group, whereas the virus growth was not. Taken together, 5-ALA showed antiviral effects against CSFV in vitro, and PPIX played a key role by inactivating virus particles extracellularly and inhibiting the replication cycle intracellularly.

Highlights

The antiviral effects of 5-aminolevulinic acid phosphate (5-ALA) and protoporphyrin IX (PPIX) against classical swine fever virus (CSFV) were evaluated by estimating the EC50 (Table S1)
The antiviral activity of 5-ALA was enhanced by the combined use of the PPIX exporter inhibitor fumitremorgin C (FTC), indicating that the intracellular accumulation of the 5-ALA metabolite PPIX
Alone suppressed virus growth both pre-treatment and post-treatment. This difference was considered to be derived from 5-ALA metabolism

Summary

Introduction

According to the official disease status by the OIE in March. CSF is endemic in a large area of Asia, Central and South America, and some Caribbean countries [4]. In these areas, routine vaccination is used to mitigate the impact of CSF outbreaks [2]. As a control strategy recommended by the OIE, slaughtering of affected pigs or prophylactic vaccination for minimizing its impact are mainly implemented instead of treatment. In CSF-free countries where pigs are expected as one of the major export items, rapid containment is applied at the highest priority to meet the requirements for maintaining their official status by the OIE.

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Conclusion